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However, there is no functional evidence showing the physiological or pathological roles of PTPIP51 in the heart. We have therefore investigated the role and mechanisms of PTPIP51 in regulating cardiac function. We found that PTPIP51 was markedly upregulated in ischemia\/reperfusion heart. Upregulation of PTPIP51 by adenovirus-mediated overexpression markedly increased the contact of mitochondria-sarcoplasmic reticulum (SR), elevated mitochondrial Ca<jats:sup>2+<\/jats:sup> uptake from SR release through mitochondrial Ca<jats:sup>2+<\/jats:sup>uniporter. Inhibition or knockdown of mitochondrial Ca<jats:sup>2+<\/jats:sup>uniporter reversed PTPIP51-mediated increase of mitochondrial Ca<jats:sup>2+<\/jats:sup> and protected cardiomyocytes against PTPIP51-mediated apoptosis. More importantly, cardiac specific knockdown of PTPIP51 largely reduced myocardium infarction size and heart injury after ischemia\/reperfusion. Our study defines a novel and essential function of PTPIP51 in the cardiac ischemia\/reperfusion process by mediating mitochondria-SR contact. Downregulation of PTPIP51 improves heart function after ischemia\/reperfusion injury, suggesting PTPIP51 as a therapeutic target for ischemic heart diseases.<\/jats:p>","DOI":"10.1038\/srep45379","type":"journal-article","created":{"date-parts":[[2017,3,27]],"date-time":"2017-03-27T10:11:57Z","timestamp":1490609517000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["PTPIP51 regulates mouse cardiac ischemia\/reperfusion through mediating the mitochondria-SR junction"],"prefix":"10.1038","volume":"7","author":[{"given":"Xue","family":"Qiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenglin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangpo","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunling","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,3,27]]},"reference":[{"key":"BFsrep45379_CR1","doi-asserted-by":"crossref","first-page":"e29","DOI":"10.1161\/circ.131.suppl_2.o29","volume":"131","author":"D Mozaffarian","year":"2015","unstructured":"Mozaffarian, D. et al. 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